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Biomedical subjects

Joanna Moncrieff

Publications and source records attributed to Joanna Moncrieff.

11 recordsLinked to original sources
PubMed2005

Rethinking models of psychotropic drug action.

Theoretical assumptions about how psychotropic drugs 'work' are rarely discussed explicitly. In a 'disease-centred model,' drugs are believed to work by acting on a disease process. In contrast, in a 'drug-centred model,' the characteristic physiological, behavioural and subjective effects of drugs are used to define drug action. The therapeutic value of a drug stems from the usefulness of these effects in clinical situations. The disease-centred model appears dominant but has weaknesses: (1) it cannot logically justify the use of drugs since major pathophysiological hypotheses were derived from selectively observed actions of drugs; (2) comparisons between drugs believed to have specific effects in certain conditions and drugs thought to have non-specific effects fail to support it; (3) outcome measures for various disorders include items responsive to non-specific drug effects; (4) studies with healthy volunteers describe characteristic drug-induced states independently of a psychiatric diagnosis; (5) animal tests show effects with agents not usually thought of as specific treatments for the conditions modelled by tests. This article offers suggestions to develop a drug-centred model and discusses its potential impact on clinical practice.

Humans↗
PubMed2003

A comparison of antidepressant trials using active and inert placebos.

In placebo-controlled antidepressant trials, there are concerns that the double blind may be breached, which may bias results. Some trials have therefore used placebos containing active substances in order to mimic the side effects of antidepressants. This study set out to examine the impact of 'unblinding' by comparing the results of a meta-analysis of a sample of trials using ordinary inert placebos with a meta-analysis of trials using active placebos. An a priori sub-group analysis of trials conducted with inpatients and outpatients was carried out. Quality was assessed using a quality assessment instrument and meta-regression analysis was conducted to explore heterogeneity. Results of meta-analysis did not differ between trials using active placebos and trials using inert ones. However, results were strongly influenced by two large trials. When these were excluded trials using inert placebos showed greater antidepressant-placebo differences than trials using active placebos. There was very high heterogeneity especially among trials using inert placebos. Meta-regression analysis showed the only significant predictor of outcome was whether trials were conducted with inpatients or outpatients. Sub-group analysis showed significant differences between antidepressants and any type of placebo in trials conducted with outpatients but not in inpatient trials. Lack of data, heterogeneity and the influence of large studies limited the analysis. The integrity of the double blind design, its effect on results and the heterogeneity between studies, require further exploration in antidepressant trials.

Antidepressive Agents↗
PubMed2003

Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination.

BACKGROUND: Although there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials. AIMS: To re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity. METHOD: Individual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity. RESULTS: Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine. CONCLUSIONS: It may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.

Antipsychotic Agents↗